肺癌是导致癌症相关死亡的主要原因。除了新颖的方法外，急需实用的策略来提高已有药物的有效性。本研究使用可吸入的干粉剂制剂对富含抗多种癌细胞系的潜力的溶解度差的驱虫药物氟苯达唑进行再利用。通过纳米沉淀法获得氟苯达唑纳米晶体，通过喷雾干燥制备干粉。通过分式因子设计，优化了喷雾干燥参数，并阐明了配方对喷雾性能的影响。通过响应面方法明确了装载限制，并通过添加20% L-亮氨酸获得15%的氟苯达唑装载量，导致氟苯达唑颗粒尺寸为388.6nm、质量中值动力学直径为2.9μm、50.3%的细颗粒剂量比、83.2%的释放量和初始溶解度的三倍。尽管该配方在A549细胞中的细胞毒性有限，但与紫杉醇结合后显示出协同作用，使IC50意外地降低了1000倍。与仅给予3个周期的紫杉醇相比，联合治疗3个周期模型增加了25%的细胞毒性阈值，剂量相同。我们的研究首次表明，口服吸入氟苯达唑纳米晶体作为辅助剂显示出很高的潜力，可以增加细胞毒性药物的效力并减少不良反应。版权所有 © 2023. Elsevier B.V. 发布。

Lung cancer is the leading cause of cancer-related death. In addition to new innovative approaches, practical strategies that improve the efficacy of already available drugs are urgently needed. In this study, an inhalable dry powder formulation is used to repurpose flubendazole, a poorly soluble anthelmintic drug with potential against a variety of cancer lineages. Flubendazole nanocrystals were obtained through nanoprecipitation, and dry powder was produced by spray drying. Through fractional factorial design, the spray drying parameters were optimized and the impact of formulation on aerolization properties was clarified. The loading limitations were clarified through response surface methodology, and a 15% flubendazole loading was feasible through the addition of 20% L-leucine, leading to a flubendazole particle size of 388.6 nm, median mass aerodynamic diameter of 2.9 μm, 50.3% FPF, emitted dose of 83.2% and triple the initial solubility. Although the cytotoxicity of this formulation in A549 cells was limited, the formulation showed a synergistic effect when associated with paclitaxel, leading to a surprising 1000-fold reduction in the IC50. Compared to 3 cycles of paclitaxel alone, a 3-cycle model combined treatment increased the threshold of cytotoxicity by 25% for the same dose. Our study suggests, for the first time, that orally inhaled flubendazole nanocrystals show high potential as adjuvants to increase cytotoxic agents' potency and reduce adverse effects.Copyright © 2023. Published by Elsevier B.V.